N-sulphonyl and N-sulphinyl amino acid amides as microbiocides

ABSTRACT

The invention relates to novel pesticidally active compounds of the general formula I                    
     as well as possible isomers and isomeric mixtures thereof, 
     wherein 
     n is a number zero or one; and 
     R 1  is C 1 -C 12 alkyl that is unsubstituted or may be substituted by C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl, C 3 -C 8 acycloalkyl, cyano, C 1 -C 6 alkoxycarbonyl, C 3 -C 8 alkenyloxycarbonyl, C 1 -C 5 alkynyloxycarbonyl; C 3 -C 8 cycloalkyl; C 2 -C 12 alkenyl: C 2 -C 12 alknyl; C 1 -C 12 haloalkyl or a group NR 11 R 12 ; wherein R 11 , and R 12  are each independently of the other hydrogen, C 1 -C 6 alkyl or together are tetra- or penta-methylene; 
     R 2  and R 3  are each independently of the other hydrogen; C 1 -C 8 alkyl; C 1 -C 8 alkyl substituted by hydroxy, C 1 -C 4 alkoxy, mercapto or by C 1 C 4 alkylthio; C 3 -C 8 alkenyl; C 3 -C 8 alkynyl; C 3 -C 8 cycloalkyl; C 3 -C 8 acycloalkyl-C 1 -C 4 alkyl or wherein the two groups R 2  and R 3  together with the carbon atom to which they are bonded form a three- to eight-membered ring; 
     R 4 , R 5 , R 6  and R 7  are identical or different and are each independently of the others hydrogen or C 1 -C 4 alkyl; 
     R 8  is C 1 -C 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl; 
     p is a number zero or one; 
     R 9  is C 1 -C 6 alkylene; and 
     A is unsubstituted or mono- or poly-substituted heteroaryl; 
     unsubstituted or mono or poly-substituted aryl containing more than 6 carbon atoms. 
     The novel compounds have plant-protecting properties and are suitable for the protection of plants against infestation by phytopathogenic microorganisms.

This application is a 371 of international application PCT/EP98/01029,filed Feb. 23, 1998.

The present invention relates to novel a-amino acid derivatives of theformula I below. It relates to the preparation of those substances andto agrochemical compositions comprising at least one of those compoundsas active ingredient. The invention relates also to the preparation ofthe said compositions and to the use of the compounds or thecompositions in controlling or preventing the infestation of plants byphytopathogenic microorganisms, especially fungi.

The invention relates to compounds of the general formula I

as well as possible isomers and mixtures of isomers thereof,

wherein

n is a number zero or one; and

R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted byC₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano,C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₁-C₆alkynyloxycarbonyl;C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl or agroup NR₁₁R₁₂; wherein R₁₁ and R₁₂ are each independently of the otherhydrogen, C₁-C₆alkyl or together are tetra- or penta-methylene;

R₂ and R₃ are each independently of the other hydrogen; C₁-C₈alkyl;C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or byC₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl;C₃-C₈cycloalkyl-C₁-C₄alkyl or wherein the two groups R₂ and R₃ togetherwith the carbon atom to which they are bonded form a three- toeight-membered ring;

R₄, R₅, R₆ and R₇ are identical or different and are each independentlyof the others hydrogen or C₁-C₄alkyl;

R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl;

p is a number zero or one;

R₉ is C₁-C₆alkylene; and

A is unsubstituted or mono- or poly-substituted heteroaryl;

unsubstituted or mono- or poly-substituted aryl containing more than 6carbon atoms.

Examples of aryl in the above-mentioned sense are:

naphthyl, anthracenyl, phenanthrenyl.

Examples of heteroaryl are:

furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl,triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl,benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl,cinnolinyl, naphthyridinyl.

Examples of substituents of those aryl or heteroaryl groups are:

alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, phenyl,phenyl-alkyl, it being possible for those groups to carry one or moreidentical or different halogen atoms; alkoxy; alkenyloxy; alkynyloxy;alkoxyalkyl; haloalkoxy, alkylthio; haloalkylthio; alkylsulfonyl;formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino;dialkylamino; carboxy; alkoxycarbonyl; alkenyloxycarbonyl;alkynyloxycarbonyl.

In the above formula I, “halogen” includes fluorine, chlorine, bromineand iodine.

The alkyl, alkenyl and alkynyl radicals may be straight-chain orbranched, and this applies also to the alkyl, alkenyl or alkynyl moietyof other alkyl-, alkenyl- or alkynyl-containing groups.

Depending upon the number of carbon atoms mentioned, alkyl on its own oras part of another substituent is to be understood as being, forexample, methyl, ethyl, propyl, butyl, pentyl and the isomers thereof,for example isopropyl, isobutyl, tert-butyl or sec-butyl. Cycloalkyl is,depending upon the number of carbon atoms mentioned, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

A haloalkyl group may have one or more (identical or different) halogenatoms, for example CHCl₂, CH₂F, CCl₃, CH₂Cl, CHF₂, CF₃, CH₂CH₂Br, C₂Cl₅,CH₂Br, CHClBr etc.

Preference is given to compounds of formula I wherein

A is naphthyl, heteroaryl that is formed from one or two five- orsix-membered rings and that may contain from 1 to 4 identical ordifferent hetero atoms selected from nitrogen, oxygen and sulfur,wherein that naphthyl or heteroaryl may carry from 1 to 4 identical ordifferent substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl,C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl,phenyl-C₁-C₄alkyl, it being possible for the hydrogen atoms of thosegroups to have been replaced by one or more identical or differenthalogen atoms; C₁-C₈alkoxy, C₃-C₈alkenyloxy, C₃-C₈alkynyloxy,C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₈haloalkoxy, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, formyl, C₂-C₈alkanoyl, hydroxy,halogen, cyano, nitro, amino, C₁-C₈alkylamino, C₁-C₈dialkylamino,carboxy, C₁-C₈alkoxy-carbonyl, C₃-C₈alkenyloxycarbonyl andC₃-C₈alkynyloxycarbonyl (sub-group A).

Within the scope of subgroup A, special mention should be made of thosecompounds of formula I wherein

A is naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl,thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl,benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, quinoxatinyl, unsubstituted or substituted byfrom 1 to 3 substituents selected from:

C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl,C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, it being possiblefor the hydrogen atoms of those groups to have been replaced by one ormore identical or different halogen atoms; C₁-C₈alkoxy, C₃-C₈alkenyloxy,C₃-C₈alkynyloxy, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₈haloalkoxy,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, formyl,C₂-C₈alkanoyl, hydroxy, halogen, cyano, nitro, amino, C₁-C₈alkylamino,C₁-C₈dialkylamino, carboxy, C₁-C₈alkoxycarbonyl, C₃-C₈alkenyloxycarbonyland C₃-C₈alkynyloxycarbonyl (subroup B).

Within the scope of subgroup B, special preference is given to a groupof compounds of formula I wherein

p is a number one;

A is naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl,thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl,benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, quinoxalinyl, unsubstituted or substituted byfrom 1 to 3 substituents selected from:

C₁-C₈alkyl, C₁-C₈haloalkyl, phenyl, phenyl-C₁-C₄alkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano andnitro (sub-group Ca).

A special group within the scope of sub-group Ca comprises compounds offormula I wherein

R₉ is —CH₂—;

A is naphthyl, furyl, thienyl, thiazolyl, oxazolyl, pyridyl.pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, unsubstituted orsubstituted by from 1 to 3 substituents selected from:

C₁-C₈alkyl, C₁-C₈haloalkyl, phenyl, phenyl-C₁-C₄alkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano andnitro (sub-group Cb).

Another especially preferred group within the scope of sub-group Bcomprises compounds of formula I wherein

n is a number one,

R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted byC₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl; C₂-C₁₂alkenyl;C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl or a group NR₁₁R₁₂;

wherein R₁₁ and R₁₂ are each independently of the other hydrogen,C₁-C₆alkyl or together are tetra- or penta-methylene;

R₂ is hydrogen;

R₃ is C₁-C₈alkyl;

C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or byC₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl;C₃-C₈cycloalkyl-C₁-C₄alkyl (sub-group Da).

Within group Da, preference is given to compounds of formula I wherein

R₁ is C₁-C₁₂alkyl, C₁-C₁₂haloalkyl or a group NR₁₁R₁₂; wherein R₁₁ andR₁₂ are each independently of the other C₁-C₆alkyl;

R₃ is C₁-C₈alkyl;

R₄ is hydrogen or C₁-C₄alkyl;

R₅, R₆ and R₇ are hydrogen;

R₈ is C₁-C₆alkyl (sub-group Db).

A preferred group within the scope of sub-group Db comprises thosecompounds of formula I wherein

R₁ is C₁-C₄alkyl or dimethylamino;

R₃ is C₃-C₄alkyl;

R₄ is hydrogen or methyl;

R₈ is C₁-C₂alkyl (sub-group Dc).

A special group within the scope of sub-group Dc is formed by compoundsof formula I wherein

R₃ is 2-propyl;

R₄ is hydrogen;

R₈ is methyl (sub-group Dd).

The presence of at least one asymmetric carbon atom and/or at least oneasymmetric sulfur atom in the compounds of formula I means that thecompounds may occur in optically isomeric forms. As a result of thepresence of a possible aliphatic C═C double bond, geometric isomerismmay also occur. The formula I is intended to include all those possibleisomeric forms and mixtures thereof.

Certain α-amino acid derivatives having a different kind of structurehave already been proposed for controlling plant-destructive fungi (forexample in EP-398 072, EP425 925, DE4 026 966, EP477 639, EP493 683,DE-4 035 851, EP487 154, EP-496 239, EP-550 788 and EP-554 729). Thosepreparations are not satisfactory, however, in respect of their action.Surprisingly, with the compound structure of formula I, new kinds ofmicrobicides having a high level of activity have been found.

The compounds of formula I can be prepared as follows:

a) by reaction of a substituted amino acid of formula II

wherein the radicals R₁, R₂ and R₃ and n are as defined above, or acarboxy-activated derivative thereof, if desired in the presence of acatalyst, if desired in the presence of an acid-binding agent and ifdesired in the presence of a diluent,

with an amine of formula III

wherein R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined above.

The amino acid derivatives of formula II required for carrying outProcess a) according to the invention are known per se or can beprepared in accordance with Process aa) described below.

The amines of formula III are novel and the invention relates alsothereto.

The amines of formula III can be prepared in accordance with Process bb)described below.

Suitable carboxy-activated derivatives of the amino acid of formula IIinclude any carboxy-activated derivatives, such as acid halides, forexample acid chlorides; also symmetrical or mixed anhydrides, forexample the mixed O-alkylcarboxylic acid anhydrides; and also activatedesters, for example p-nitrophenyl esters or N-hydroxysuccinimide esters,and activated forms of the amino acid produced in situ usingcondensation agents, e.g. dicyclo-hexylcarbodiimide,carbonyldiimidazole,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(pentaethylene)uroniumhexafluorophosphate,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(tetramethylene)uroniumhexafluorophosphate, (benzotriazol-1-yloxy)-tripyrrolidinophosphoniumhexafluorophosphate,(benzotriazol-1-yloxy)-tris(dimethylamino)phosphoniumhexafluorophosphate orO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.

The acid halides corresponding to the amino acid of formula II can beprepared by reacting the amino acid of formula II in a generally knownmanner with a halogenating agent, for example phosphorus pentachloride,thionyl chloride or oxalyl chloride.

The mixed anhydrides corresponding to the amino acid of formula II canbe prepared by reacting the amino acid of formula II with a chloroformicacid ester, for example a chloroformic acid alkyl ester, preferablyisobutyl chloroformate, if desired in the presence of an acid-bindingagent, such as an inorganic or organic base, for example a tertiaryamine, e.g. triethylamine, pyridine, N-methylpiperidine orN-methylmorpholine.

The reaction of the amino acid of formula II, or of a carboxy-activatedderivative of the amino acid of formula II, with an amine of formula IIIis carried out in an inert diluent, such as an aromatic, non-aromatic orhalogenated hydrocarbon, for example a chlorinated hydrocarbon, e.g.methylene chloride or toluene; a ketone, e.g. acetone; an ester, e.g.ethyl acetate; an amide, e.g. dimethylformamide; a nitrile, e.g.acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane, diethyl etheror tert-butyl methyl ether; or in a mixture of those inert diluents, ifdesired in the presence of an acid-binding agent, such as an inorganicor organic base, for example a tertiary amine, e.g. triethylamine,pyridine, N-methylpiperidine or N-methyl-morpholine, at temperatures offrom −80 to +150° C., preferably from −40 to +40° C.

b) by oxidation of a compound of formula I′

wherein R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined above, with theproviso that none of the substituents R₁, R₂, R₃ and A contains a thiolor alkylthio group.

Suitable oxidising agents include both organic oxidising agents, such asalkyl hydro-peroxides, for example cumyl hydroperoxide, and inorganicoxidising agents, such as peroxides, for example hydrogen peroxide, andtransition metal oxides, for example chromium trioxide, and transitionmetal oxide salts, for example potassium permanganate, potassiumdichromate or sodium dichromate.

The reaction of a compound of formula I′ with the oxidising agent iscarried out in an inert diluent, such as water or a ketone, for exampleacetone, or in a mixture of those inert diluents, optionally in thepresence of an acid or optionally in the presence of a base, attemperatures of from −80 to +150° C.

c) by reaction of a compound of formula IV

wherein n, R₁, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ are as defined above, witha compound of formula V

Y—(R₉)p—A  V

wherein R₉, p and A are as defined above and wherein Y is a leavinggroup. Suitable leaving groups include halides, for example chlorides orbromides, and sulfonates, for example tosylates, mesylates or triflates.

The reaction of the compounds of formula IV with compounds of formula Vis carried out in an inert diluent. The following may be mentioned asexamples: aromatic, non-aromatic or halogenated hydrocarbons, e.g.toluene or methylene chloride; ketones, e.g. acetone; esters, e.g. ethylacetate; amides, e.g. dimethylformamide; nitrites, e.g. acetonitrile;ethers, e.g. tetrahydrofuran; dioxane, diethyl ether or tert-butylmethyl ether; alcohols, e.g. methanol, ethanol, n-butanol, isopropanolor tert-butanol; dimethyl sulfoxide; or water; or mixtures of thoseinert diluents. The reaction of the compounds of formula IV withcompounds of formula V is carried out if desired in the presence of anacid-binding agent. Suitable acid-binding agents include inorganic ororganic bases, for example alkali metal or alkaline earth metalhydroxides, alcoholates or carbonates, e.g. sodium hydroxide, potassiumhydroxide, sodium methanolate, potassium methanolate, sodium ethanolate,potassium ethanolate, sodium tert-butanolate, potassium tert-butanolate,sodium carbonate or potassium carbonate. The temperatures are from −80to +200° C., preferably from 0 to +120° C.

The compounds of formula IV can be prepared in accordance with Processcc).

d) by reaction of a sulfonic acid or sulfinic acid, or of a sulfonicacid or sulfinic acid derivative, of formula VI

wherein R₁ and n are as defined above and wherein X is an OH group or aleaving group, respectively, with an amine of formula VII

wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined above.

The invention relates also to the compounds of formula VII and to theirpreparation.

The sulfonic acid or sulfinic acid, or sulfonic acid or sulfinic acidderivatives, of formula VI required for Process d) are known per se. Theamines of formula VII also required are novel and the invention relatesalso thereto; they can be prepared in accordance with Process dd) below.

Suitable sulfonic acid or sulfinic acid derivatives of formula VIinclude any compounds wherein X is a leaving group, such as sulfonicacid halides or sulfinic acid halides, e.g. sulfochlorides or sulfinicacid chlorides; also symmetrical of mixed anhydrides; and also activatedforms of sulfonic acid or sulfinic acid produced in situ usingcondensation agents, such as dicyclohexylcarbodiimide orcarbonyldiimidazole.

The reaction of the sulfonic acid or sulfinic acid, or of the sulfonicacid or sulfinic acid derivative, of formula VI with an amine of formulaVII is carried out in an inert diluent, such as an aromatic,non-aromatic or halogenated hydrocarbon, for example a chlorinatedhydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone;an ester, e.g. ethyl acetate; an amide, e.g. dimethylformamide; anitrile, e.g. acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane,diethyl ether or tert-butyl methyl ether; or water; or in a mixture ofthose inert diluents, if desired in the presence of an acid-bindingagent, such as an inorganic or organic base; for example an alkali metalor alkaline earth metal hydroxide or carbonate, e.g. sodium hydroxide,potassium hydroxide, sodium carbonate or potassium carbonate, or, forexample, a tertiary amine, e.g. triethylamine, pyridine,N-methylpiperidine or N-methyl-morpholine, at temperatures of from −80to +150° C., preferably from −20 to +60° C.

aa) The required amino acid derivatives of formula II can be prepared byreaction of an amino acid of formula VIII

with a sulfonic acid or sulfinic acid, or with a sulfonic acid orsulfinic acid derivative, of formula VI

wherein R₁, R₂, R₃ and n are as defined above and wherein X is an OHgroup pr a leaving group, respectively.

The sulfonic acid or sulfinic acid, or sulfonic acid or sulfinic acidderivative, of formula VI required for Process aa) and the amino acidsof formula VIII are known per se.

Suitable sulfonic acid or sulfinic acid derivatives of formula VIinclude any compounds wherein X is a leaving group, such as sulfonicacid halides or sulfinic acid halides, e.g. sulfochlorides or sulfinicacid chlorides; also symmetrical or mixed anhydrides; and also activatedforms of sulfonic acid or sulfinic acid produced in situ usingcondensation agents, such as dicyclohexylcarbodiimide orcarbonyldiimidazole.

The reaction of the sulfonic acid or sulfinic acid, or of the sulfonicacid or sulfinic acid derivative, of formula VI with an amine of formulaVIII is carried out in an inert diluent, such as an aromatic,non-aromatic or halogenated hydrocarbon, for example a chlorinatedhydrocarbon, e.g. methylene chloride or toluene; a ketone, e.g. acetone;an ester, e.g. ethyl acetate; an amide, e.g. dimethylformamide; anitrile, e.g. acetonitrile; or an ether, e.g. tetrahydrofuran, dioxane,diethyl ether or tert-butyl methyl ether; or water; or in a mixture ofthose inert diluents, if desired in the presence of an acid-bindingagent, such as an inorganic or organic base; for example an alkali metalor alkaline earth metal hydroxide or carbonate, e.g. sodium hydroxide,potassium hydroxide, sodium carbonate or potassium carbonate, or, forexample, a tertiary amine, e.g. triethylamine, pyridine,N-methylpiperidine or N-methyl-morpholine, at temperatures of from −80to +150° C., preferably from −20 to +60° C.

bb) The amines of formula III can be prepared in accordance with thefollowing process variants:

Step A comprises the alkylation of a phenol with a compound of formulaV. The reaction is carried out as described under Process c).

Step B comprises the reaction of an aromatic aldehyde with nitromethane.The reaction of the two reactants is carried out in an inert diluent,such as an organic carboxylic acid, for example acetic acid, optionallyin the presence of the ammonium salt of that carboxylic acid, forexample ammonium acetate, at temperatures of from 0° to +200° C.

Step C comprises the reduction of an unsaturated nitrogen compound. Thereaction is carried out in an inert diluent, such as an ether, forexample diethyl ether, dioxane or tetrahydrofuran, or an alcohol, forexample methanol, ethanol or isopropanol, with a boron hydride, a boronhydride complex, for example the complex of boron hydride andtetrahydrofuran, an alkali metal borohydride, alkali metal aluminiumhydride, for example lithium aluminium hydride, or an aluminiumalkoxyhydride, or with hydrogen optionally in the presence of atransition metal or a transition metal compound, for example nickel, attemperatures of from −50° to +250° C.

Step D comprises the reaction of an aldehyde or a ketone withhydroxylamine or a hydroxylamine salt. The reaction is carried out in aninert diluent, such as an alcohol, for example methanol, ethanol orisopropanol, an ether, for example diethyl ether, dioxane ortetrahydrofuran, an amide, for example dimethylformamide, or in water,or in a mixture of those inert diluents, optionally in the presence ofan organic or inorganic base, such as a tertiary amine, for exampletriethylamine, a nitrogen-containing heteroaromatic compound, forexample pyridine, an alkali or alkaline earth metal carbonate orhydrogen carbonate, for example sodium carbonate or potassium carbonate,at temperatures of from −20° to +150° C.

Step E comprises the hydrolysis of a lower alkyl ester. The reaction iscarried out in an inert diluent, such as an alcohol, for examplemethanol, ethanol or isopropanol, an ether, for example diethyl ether,dioxane or tetrahydrofuran, a halogenated hydrocarbon, for exampledichloromethane, or in water or in a mixture of those inert diluents,optionally in the presence of a base, such as an alkali or alkalineearth metal hydroxide, for example lithium hydroxide, sodium hydroxideor potassium hydroxide, or in the presence of an acid, for examplesulfuric acid, hydrochloric acid or trifluoroacetic acid, attemperatures of from −20° to +160° C.

Step F comprises the reaction of a carboxylic acid or an activatedderivative of that carboxylic acid with hydrazoic acid or with a salt ofthat acid. Suitable carboxy-activated derivatives include anycarboxy-activated derivatives, such as acid halides, for example acidchlorides; and also symmetric or mixed anhydrides, for example the mixedO-alkylcarboxylic acid anhydrides. Suitable salts of hydrazoic acidinclude, for example, alkali or alkaline earth metal azides, for examplesodium azide. The reaction is carried out in a diluent, such as ahydrocarbon, for example toluene or xylene, a halogenated hydrocarbon,for example chloroform, an ether, for example dioxane, a ketone, forexample acetone or methyl ethyl ketone, an alcohol, for exampletert-butanol, or in water, or in a mixture of those diluents, optionallyin the presence of an acid, such as an inorganic acid, for examplesulfuric acid or hydrochloric acid, at temperatures of from 40° to +200°C.

cc) The compounds of formula IV can be prepared by reaction of asubstituted amino acid of formula II

wherein the radicals R₁, R₂ and R₃ and n are as defined above, or acarboxy-activated derivative thereof, if desired in the presence of acatalyst, if desired in the presence of an acid-binding agent and ifdesired in the presence of a diluent,

with a compound of the general formula XII, or an acid addition salt ofthat compound,

wherein R₄, R₅, R₆, R₇ and R₈ are as defined above.

Suitable carboxy-activated derivatives of the amino acid of formula IIinclude any carboxy-activated derivatives, such as acid halides, forexample acid chlorides; also symmetrical or mixed anhydrides, forexample the mixed O-alkylcarboxylic acid anhydrides; and also activatedesters, for example p-nitrophenyl esters or N-hydroxysuccinimide esters,and activated forms of the amino acid produced in situ usingcondensation agents, e.g. dicyclohexylcarbodiimide, carbonyldiimidazole,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(pentamethylene)uroniumhexafluorophosphate,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(tetramethylene)uroniumhexafluorophosphate, (benzotriazol-1-yloxy)-tripyrrolidinophosphoniumhexafluorophosphate,(benzotriazol-1-yloxy)-tris(dimethylamino)phosphoniumhexafluorophosphate orO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate.

The acid halides corresponding to the amino acid of formula II can beprepared by reacting the amino acid of formula II in a generally knownmanner with a halogenating agent, for example phosphorus pentachloride,thionyl chloride or oxalyl chloride.

The mixed anhydrides corresponding to the amino acid of formula II canbe prepared by reacting the amino acid of formula II with a chloroformicacid ester, for example a chloroformic acid alkyl ester, preferablyisobutyl chloroformate, if desired in the presence of an acid-bindingagent, such as an inorganic or organic base, for example a tertiaryamine, e.g. triethylamine, pyridine, N-methylpiperidine orN-methylmorpholine.

The reaction of the amino acid of formula II, or of a carboxy-activatedderivative of the amino acid of formula II, with a compound of thegeneral formula XII is carried out in an inert diluent, such as anaromatic, non-aromatic or halogenated hydrocarbon, for example achlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone,e.g. acetone; an ester, e.g. ethyl acetate; an amide, e.g.dimethylformamide; a nitrile, e.g. acetonitrile; or an ether, e.g.tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; orin a mixture of those inert diluents, if desired in the presence of anacid-binding agent, e.g. an inorganic or organic base, for example atertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine orN-methylmorpholine, at temperatures of from −80 to +150° C., preferablyfrom −40 to +40° C.

dd) The required amines of formula VII can be prepared in accordancewith the following reaction sequence

In a first step, an amino acid derivative of the general formula XIII,or a carboxy-activated derivative thereof, is reacted, if desired in thepresence of a catalyst, if desired in the presence of an acid-bindingagent and if desired in the presence of a diluent, with an amine of thegeneral formula XII.

Suitable carboxy-activated derivatives of the amino acid of formula XIIIinclude any carboxy-activated derivatives, such as acid halides, forexample acid chlorides; also symmetrical or mixed anhydrides, forexample the mixed O-alkylcarboxylic acid anhydrides; and also activatedesters, for example p-nitrophenyl esters or N-hydroxysuccinimide esters,and activated forms of the amino acid produced in situ usingcondensation agents, e.g. dicyclohexylcarbodiimide, carbonyldiimidazole,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(pentamethylene)uroniumhexafluorophosphate,O-(benzotriazol-1-yl)-N,N,N′,N′-bis(tetramethylene)uroniumhexafluorophosphate, (benzotriazol-1-yloxy)-tripyrrolidinophosphoniumhexafluorophosphate,(benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphateor O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate.

The acid halides corresponding to the amino acid of formula XIII can beprepared by reacting the amino acid of formula XIII in a generally knownmanner with a halogenating agent, for example phosphorus pentachloride,thionyl chloride or oxalyl chloride.

The mixed anhydrides corresponding to the amino acid of formula XIII canbe prepared by reacting the amino acid of formula XIII with achloroformic acid ester, for example a chloroformic acid alkyl ester,preferably isobutyl chloroformate, if desired in the presence of anacid-binding agent, such as an inorganic or organic base, for example atertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine orN-methylmorpholine.

The reaction of the amino acid of formula XIII, or of acarboxy-activated derivative of the amino acid of formula XIII, with anamine of formula XII is carried out in an inert diluent, such as anaromatic, non-aromatic or halogenated hydrocarbon, for example achlorinated hydrocarbon, e.g methylene chloride or toluene; a ketone,e.g. acetone; an ester, e.g. ethyl acetate; an amide, e.g.dimethylformamide; a nitrile, e.g. acetonitrile; or an ether, e.g.tetrahydrofuran, dioxane, diethyl ether or tert-butyl methyl ether; orin a mixture of those inert diluents, if desired in the presence of anacid-binding agent, e.g. an inorganic or organic base, for example atertiary amine, e.g. triethylamine, pyridine, N-methylpiperidine orN-methylmorpholine, at temperatures of from −80 to +150° C., preferablyfrom 40 to +40° C.

In a second step, a compound of formula XIV is reacted with a compoundof formula V.

The reaction of a compound of formula XIV with a compound of formula Vis carried out in an inert diluent. The following may be mentioned asexamples: aromatic, non-aromatic or halogenated hydrocarbons, forexample toluene or methylene chloride; ketones, for example acetone;esters, for example ethyl acetate; amides, for exampledimethylformamide; nitriles, for example acetonitrile; ethers, forexample tetrahydrofuran, dioxane, diethyl ether or tertbutyl methylether; alcohols, for example methanol, ethanol, n-butanol, isopropanolor tertbutanol; dimethyl sulfoxide or water or mixtures of those inertdiluents. The reaction of the compounds of formula XIV with compounds offormula V is carried out if desired in the presence of an acid-bindingagent. Suitable acid-binding agents include inorganic or organic bases,for example alkali or alkaline earth metal hydroxides, alcoholates orcarbonates, e.g. sodium hydroxide, potassium hydroxide, sodiummethanolate, potassium methanolate, sodium ethanolate, potassiumethanolate, sodium tert-butanolate, potassium tert-butanolate, sodiumcarbonate or potassium carbonate. The temperatures are from −80 to +200°C., preferably from 0 to 120° C.

In a third step, compounds of formula XV are subjected to acidhydrolysis. The reaction of a compound of formula XV with an inorganicor organic acid, for example a mineral acid, e.g. hydrochloric acid orsulfuric acid, or a carboxylic acid, e.g. acetic acid or trifluoroaceticacid, or a sulfonic acid, e.g. methanesulfonic acid or p-toluenesulfonicacid, is carried out if desired in an inert diluent, such as anaromatic, non-aromatic or halogenated hydrocarbon, for example achlorinated hydrocarbon, e.g. methylene chloride or toluene; a ketone,e.g. acetone; an ester, e.g. ethyl acetate; an ether, e.g.tetrahydrofuran or dioxane; or water, at temperatures of from −40 to+150° C. If desired, it is also possible to use mixtures of differentacids and of different inert diluents, or the acid itself may serve asthe diluent.

The compounds of formula I are oils or solids at room temperature thatare distinguished by valuable microbicidal properties. They can be usedin the agricultural sector or related fields preventively and curativelyin the control of plant-destructive microorganisms. The compounds offormula I according to the invention are distinguished at low rates ofconcentration not only by outstanding microbicidal, especiallyfungicidal, activity but also by being especially well tolerated byplants.

Surprisingly, it has now been found that the compounds of formula I havefor practical purposes a very advantageous biocidal spectrum in thecontrol of phytopathogenic microorganisms, especially fungi. Theypossess very advantageous curative and preventive properties and areused in the protection of numerous crop plants. With the compounds offormula I it is possible to inhibit or destroy pests that occur onvarious crops of useful plants or on parts of such plants (fruit,blossom, leaves, stems, tubers, roots), while parts of the plants whichgrow later also remain protected, for example, against phytopathogenicfungi.

The novel compounds of formula I prove to be effective against specificgenera of the fungus class Fungi imperfecti (e.g. Cercospora),Basidiomycetes (e.g. Puccinia) and Ascomycetes (e.g. Erysiphe andVenturia) and especially against Oomycetes (e.g. Plasmopara,Peronospora, Pythium and Phytophthora). They therefore represent inplant protection a valuable addition to the compositions for controllingphytopathogenic fungi. The compounds of formula I can also be used asdressings for protecting seed (fruit, tubers, grains) and plant cuttingsfrom fungal infections and against phytopathogenic fungi that occur inthe soil.

The invention relates also to compositions comprising compounds offormula I as active ingredient, especially plant-protectingcompositions, and to the use thereof in the agricultural sector orrelated fields.

In addition, the present invention includes the preparation of thosecompositions, wherein the active ingredient is homogeneously mixed withone or more of the substances or groups of substances described herein.Also included is a method for the treatment of plants which comprisesthe application of the novel compounds of formula I or the novelcompositions.

Target crops to be protected within the scope of this inventioncomprise, for example, the following species of plants: cereals (wheat,barley, rye, oats, rice, maize, sorghum and related species); beet(sugar beet and fodder beet); pomes, stone fruit and soft fruit (apples,pears, plums, peaches, almonds, cherries, strawberries, raspberries andblackberries), leguminous plants (beans, lentils, peas, soybeans); oilplants (rape, mustard, poppy, olives, sunflowers, coconut, castor oilplants, cocoa beans, groundnuts); cucurbitaceae (marrows, cucumbers,melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges,lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus,cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae(avocado, cinnamon, camphor) and plants such as tobacco, nuts, coffee,sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants,and also ornamentals.

The compounds of formula I are normally applied in the form ofcompositions and can be applied to the area or plant to be treatedsimultaneously or in succession with other active ingredients. Thosefurther active ingredients may be fertilisers, micronutrient donors orother preparations that influence plant growth. It is also possible touse selective herbicides or insecticides, fungicides, bactericides,nematicides, molluscicides or mixtures of several of those preparations,if desired together with further carriers, surfactants or otherapplication-promoting adjuvants customarily employed in formulationtechnology.

The compounds of formula I can be mixed with other fungicides, with theresult that in some cases unexpected synergistic effects are obtained.Especially preferred mixing partners are azoles, such as propiconazole,difenoconazole, cyproconazole, epoxiconazole, tebuconazole,tetraconazole, fenbuconazole, metconazole, bromuconazole; alsofenpropidine, fenpropimorph, cyprodinil, pyrimethanil,benzo-1,2,3thiadiazole-7-carbonothioic acid S-methyl ester, andstrobilurins, such as azoxystrobin and cresoxime-methyl.

Suitable carriers and surfactants may be solid or liquid and correspondto the substances ordinarily employed in formulation technology, suchas, e.g. natural or regenerated mineral substances, solvents,dispersants, wetting agents, tackifiers, thickeners, binders orfertilisers.

A preferred method of applying a compound of formula I, or anagrochemical composition comprising at least one of those compounds, isapplication to the foliage (foliar application), the frequency and therate of application depending upon the risk of infestation by thepathogen in question. The compounds of formula I may also be applied toseed grains (coating) either by impregnating the seeds with a liquidformulation of the active ingredient or by coating them with a solidformulation.

The compounds of formula I are used in unmodified form or, preferably,together with the adjuvants conventionally employed in formulationtechnology, and are for that purpose advantageously formulated in knownmanner e.g. into emulsifiable concentrates, coatable pastes, directlysprayable or dilutable solutions, dilute emulsions, wettable powders,soluble powders, dusts, granules, and by encapsulation in e.g. polymersubstances. As with the nature of the compositions, the methods ofapplication, such as spraying, atomising, dusting, scattering, coatingor pouring, are chosen in accordance with the intended objectives andthe prevailing circumstances.

Advantageous rates of application are normally from 1 g to 2 kg ofactive ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kga.i./ha, especially from 25 g to 750 g a.i./ha. When used as seeddressings, rates of from 0.001 g to 1.0 g of active ingredient per kg ofseed are advantageously used.

The formulations, i.e. the compositions, preparations or mixturescomprising the corn-pound(s) (active ingredient(s)) of formula I and,where appropriate, a solid or liquid adjuvant, are prepared in knownmanner, e.g. by homogeneously mixing and/or grinding the activeingredient with extenders and adjuvants customary in agriculturaltechnology, e.g. solvents, solid carriers and, where appropriate,surface-active compounds (surfactants).

Further surfactants customarily used in formulation technology will beknown to the person skilled in the art or can be found in the relevanttechnical literature.

The agrochemical compositions usually comprise 0.01 to 99% by weight,preferably 0.1 to 95% by weight, of a compound of formula I, 99.99 to 1%by weight, preferably 99.9 to 5% by weight, of a solid or liquidadjuvant, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of asurfactant.

Whereas commercial products will preferably be formulated asconcentrates, the end user will normally employ dilute formulations.

The compositions may also comprise further ingredients, such asstabilisers, antifoams, viscosity regulators, binders and tackifiers, aswell as fertilisers or other active ingredients for obtaining specialeffects.

The Examples which follow illustrate the invention described above,without limiting the scope thereof in any way. Temperatures are given indegrees Celsius.

PREPARATION EXAMPLES FOR COMPOUNDS OF FORMULA I: Example 1.1

(S)-2Methylsulfonyl-amino)-3methyl-butyric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide

A mixture of 1.3 g of (S)-methanesulfonic acidN-(2-methyl-1-carboxy)-propylamide, 2.0 g of2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamide, 2.9 g of(benzotriazol-1-yl-oxy)-tris(dimethylamino)phosphoniumhexafluorophosphate and 3.4 ml of N-ethyl-diisopropylamine is stirred in30 ml of N,N-dimethylformamide at room temperature for 2 hours. Thereaction mixture is introduced into 300 ml of water. Extraction iscarried out twice using 300 ml of ethyl acetate each time. The organicphases are washed once with 100 ml of saturated sodium chloridesolution, combined, dried over magnesium sulfate and concentrated,yielding (S)-2-(methylsulfonyl-amino)-3-methyl-butyric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide, whichcan be purified by chromatography on silica gel with ethylacetate/n-hexane=2:1 and recrystallisation from ethyl acetate/n-hexane.M.p. 153-157° C.

The Examples listed in Table 1 are obtained in an analogous manner.

TABLE 1

Conf. Phys. Comp. at data No. α-C R₁ R₂ R₃ m.p. ° C. 1.1 (S) methyl2-propyl

153-157 1.2 (S) N(CH₃)₂ 2-propyl

oil 1.3 (S) n-propyl 2-propyl

1.4 (S) 3-Cl-propyl 2-propyl

134-138 1.5 (S) n-butyl 2-propyl

1.6 (S) methyl 2-Me-2- propyl

1.7 (S) ethyl 2-Me-2- propyl

141-144 1.8 (S) N(CH₃)₂ 2-Me-2- propyl

1.9 (S) ethyl ethyl

1.10 (R, S) ethyl cyclohexyl 1.11 (R, S) ethyl cyclopropyl

1.12 (S) ethyl 2-butyl

131-134 1.13 (S) ethyl 2-MeS-ethyl

104-106 1.14 (S) propyl 2-propyl

130-131 1.15 (S) isopropyl 1-OH-ethyl

109-112 1.16 (S) 2-Me-2- propen-1-yl 2-propyl

135-137 1.17 (S) N(CH₃)₂ 2-propyl

120-121

Example 2.1

(S)-2-(Ethylsulfonylamino)-3-methyl-butyric acidN-{2-[4-(5-chloro-thiophen-2-ylmethoxy)-3-methoxy-phenyl]-ethyl}-amide

A mixture of 2.0 g of (S)-2-(ethylsulfonylamino)-3methyl-butyric acidN-[2-(4hydroxy-3-methoxy-phenyl)-ethyl]-amide, 1.2 g of2-chloro-5-chloromethylthiophene and 12 ml of a 1 M sodium methanolatesolution in methanol (prepared beforehand by dissolution of 23 g ofsodium in 1 liter of methanol) is heated at reflux in 30 ml of methanolfor 16 hours. After cooling, the reaction mixture is introduced into 300ml of 2N sodium hydroxide solution. Extraction is carried out twiceusing 400 ml of tert-butyl methyl ether each time. The organic phasesare washed once with 100 ml of 2N sodium hydroxide solution and oncewith 100 ml of saturated sodium chloride solution, dried over magnesiumsulfate and concentrated, yielding(S)-2-(ethylsulfonylamino)-3-methyl-butyric acidN-{2-[4-(5-chloro-thiophen-2-yl-methoxy)-3-methoxy-phenyl]-ethyl}-amide,which can be purified by chromatography on silica gel with ethylacetate/n-hexane 1:1 and recrystallisation from ethyl acetate/n-hexane,m.p. 124-127° C.

The Examples listed in Table 2 are obtained in an analogous manner.

TABLE 2

Phys. Conf. data No. α-C n R₁ R₂ R₃ R₄ -(R₉)p-A m.p. ° C. 2.1. (S) 1ethyl H 2- propyl H

124-127 2.2. (S) 1 methyl H 2- propyl H

125-145 2.3. (S) 1 methyl H 2- propyl CH₃

2.5. (S) 1 trifluoromethyl H 2- propyl H

2.6. (S) 1 propyl H 2- propyl H

2.7. (S) 0 2-propyl H 2- propyl H

2.8. (S) 1 2-propyl H 2- propyl H

2.9. (S) 1 2-butyl H 2- propyl H

2.10. (S) 0 cyclohexyl H 2- propyl H

2.11. (S) 1 3-chloropropyl H 2- propyl H

2.12. (S) 1 N(CH₃)₂ H 2- propyl H

2.13. (S) 1 NH(CH₃) H 2- propyl H

2.14. (S) 1 ethyl H ethyl H

2.15. (S) 1 methyl H ethyl H

2.16. (R, S) 1 ethyl H cyclo- propyl H

107-109 2.17. (R, S) 1 ethyl H allyl H

2.18 (S) 1 ethyl tetra- methylene H

2.19. (S) 0 2-butyl propyl H 2- H

2.20. (S) 1 ethyl H 2-butyl H

2.21. (R, S) 1 ethyl H cyclo- propyl methyl H

2.22. (S) 1 CH₂═C(CH₃)—CH₂ H 2- propyl H

2.23. (S) 1

H 2- propyl H

2.24. (S) 1 ethyl H methyl H

2.25. (S) 1 octyl H 2- propyl H

2.26. (S) 1 ethyl H 2- propyl H

2.27. (S) 1 ethyl H 2- propyl H

2.28. (S) 1 ethyl H 2- propyl H

2.29. (S) 1 ethyl H 2- propyl H

2.30. (S) 1 ethyl H 2- propyl H

134-137 2.31. (S) 1 ethyl H 2- propyl H

126-128 2.32. (S) 1 ethyl H 2- propyl H

2.33. (S) 1 ethyl H 2- propyl H

2.34. (S) 1 ethyl H 2- propyl H

2.35 (S) 1 ethyl H 2- propyl H

2.36. (S) 1 ethyl H 2- propyl H

2.37. (S) 1 ethyl H 2- propyl H

2.38. (S) 1 ethyl H 2- propyl H

2.39. (S) 1 ethyl H 2- propyl H

123-126 2.40. (S) 1 ethyl H 2- propyl H

2.41. (S) 1 ethyl H 2- propyl H

126-132 2.42. (S) 1 ethyl H 2- propyl H

2.43. (S) 1 ethyl H 2- propyl H

2.44. (S) 1 ethyl H 2- propyl H

118-121 2.45. (S) 1 ethyl H 2- propyl H

134-137 2.46. (S) 1 ethyl H 2- propyl H

2.47. (S) 1 ethyl H 2- propyl H

2.48. (S) 1 ethyl H 2- propyl H

141-144 2.49. (S) 1 methyl H 2- propyl H

130-135 2.50. (S) 1 ethyl H 2- propyl H

141-143 2.51. (S) 1 ethyl H 2- propyl H

168-171 2.52. (S) 1 ethyl H 2- propyl H

2.53. (S) 1 ethyl H 2- propyl H

2.54. (S) 1 ethyl H 2- propyl H

2.55. (S) 1 ethyl H 2- propyl H

152-155 2.56. (S) 1 ethyl H 2- propyl H

2.57. (S) 1 ethyl H 2- propyl H

142-145 2.58. (S) 1 ethyl H 2- propyl H

2.59. (S) 1 ethyl H 2- propyl H

2.60. (S) 1 ethyl H 2- propyl H

2.61. (S) 1 ethyl H 2- propyl H

2.62. (S) 1 ethyl H 2- propyl H

2.63. (S) 1 ethyl H 2- propyl H

2.64. (S) 1 ethyl H 2- propyl H

2.65. (S) 1 ethyl H 2- propyl H

2.66. (S) 1 ethyl H 2- propyl H

2.67. (S) 1 ethyl H 2- propyl H

2.68. (S) 1 ethyl H 2- propyl H

2.69. (S) 1 ethyl H 2- propyl H

2.70. (S) 1 ethyl H 2- propyl H

2.71. (S) 1 ethyl H 2- propyl H

152-154 2.72. (S) 1 ethyl H 2- propyl H

2.73. (S) 1 ethyl H 2- propyl H

2.74. (S) 1 ethyl H 2- propyl H

2.75. (S) 1 ethyl H 2- propyl H

2.76. (S) 1 ethyl H 2- propyl H

2.77. (S) 1 ethyl H 2- propyl H

133-136 2.78. (S) 1 ethyl H 2- propyl H

2.79. (S) 1 ethyl H 2- propyl H

2.80. (S) 1 ethyl H 2- propyl H

2.81. (S) 1 ethyl H 2- propyl H

2.82. (S) 1 ethyl H 2- propyl H

2.83 (S) 1 ethyl H 2- propyl H

2.84 (S) 1 ethyl H 2- propyl H

2.85 (S) 1 ethyl H 2- propyl H

2.86 (S) 1 ethyl H 2-Me- 2-pro- pyl H

oil 2.87 (R, S) 1 ethyl H cyclo- hexyl H

147-148 2.88 (S) 1 ethyl H 2- propyl H

151-152 2.89 (S) 1 ethyl H 2- propyl H

oil 2.90 (S) 1 ethyl H ethyl H

171-178

Example 3.1

(2S,3S)-2-(Butylsulfonyl-amino)-3methyl-valeric acidN-{2-[3methoxy-4-(naphthalen-1-yl-methoxy)-phenyl]-ethyl}-amide

3.4 g of (2S,3S)-2-amino-3-methyl-valeric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide and 1.2ml of triethylamine are placed in 50 ml of dioxane at room temperature.1.0 ml of n-butylsulfonyl chloride is added thereto. Stirring is carriedout for 16 hours. The reaction mixture is introduced into 200 ml ofwater. Extraction is carried out twice using 200 ml of ethyl acetateeach time. The organic phases are washed once with 200 ml of saturatedsodium chloride solution, combined, dried over magnesium sulfate andconcentrated, yielding (2S,3S)-2-(butylsulfonyl-amino)-3-methyl-valericacid N-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]ethyl}-amide,which can be purified by chromatography on silica gel with ethylacetatein-hexane =1:1, in the form of an oil.

Preparation Example for Intermediates:

Example 5.1.

(R,S)-Methanesulfonic acid N-(2-methyl-1-carboxy)-propyl-amide

30 g of D,L-valine and 10.2 g of sodium hydroxide are dissolved in 250ml of water and, with stirring, cooled to 0° C. There are then addeddropwise to that solution, simultaneously over a period of one hour, asolution of 10.2 g of sodium hydroxide in 250 ml of water and a solutionof 20 ml of methanesulfonic acid chloride in 250 ml of toluene. Stirringof the reaction mixture is continued first at 0° C. for 2 hours and thenat room temperature for 16 hours. The toluene phase is then separatedoff in a separating funnel and discarded. The aqueous phase is adjustedto pH <3 with conc. hydrochloric acid. Extraction is carried out twiceusing 1000 ml of diethyl ether each time. The organic phases are washedtwice using 200 ml of saturated sodium chloride solution each time,combined, dried over magnesium sulfate and concentrated, yielding(R,S)-methanesulfonic acid N-(2-methyl-1-carboxy)-propylamide, which canbe purified by recrystallisation from ethyl acetate/hexane, m.p. 90-91°C.

The Examples listed in Table 5 are obtained analogously to the aboveExample.

TABLE 5

Phys. Conf. data No. n R₁ R₂ R₃ α-C m.p. ° C. 5.1 1 methyl H 2-propyl(R, S) 90-91 5.2 1 methyl H 2-propyl (S) oil 5.3 1 Me₂N- H 2-propyl (R,S) oil 5.4 1 Me₂N H 2-propyl (S) resin 5.5 0 methyl H 2-propyl (R, S)5.6 0 2-propyl H 2-propyl (R, S) 5.7 0 2-methyl-2-propyl H 2-propyl (R,S) 5.8 0 methyl H 2-propyl (S) 5.9 0 2-propyl H 2-propyl (S) 5.10 02-methyl-2-propyl H 2-propyl (S) 5.11 0 cyclohexyl H 2-propyl (S) 5.12 1ethyl H 2-propyl (S) resin 5.13 1 Me₂N H 2-butyl (S) resin 5.14 1 ethylH 1-(tert-butyl)- (S) oil oxy-ethyl 5.15 1 methyl H ethyl (S) resin 5.181 ethyl H ethyl (S) resin 5.17 1 methyl methyl methyl — 109-111 5.18 1methyl tetra- methylene 5.19 1 propyl H 2-propyl (S) oil 5.20 1 2-propylH 2-propyl (S) oil 5.21 1 3-chloropropyl H 2-propyl (S) 108-109 5.22 1ethenyl H 2-propyl (S) 5.23 1 butyl H 2-propyl (S) 5.24 1 isobutyl H2-propyl (S) 5.25 1 allyl H 2-propyl (S) 5.26 1 2-methyl-2-propen- H2-propyl (S) 120-122 1-yl 5.27 1 diethylamino H 2-propyl (S) 5.28 1methylamino H 2-propyl (S) 5.29 1 methyl H ethyl (S) 5.30 1 ethyl Hethyl (S) 5.31 1 propy H ethyl (S) 5.32 1 2-propyl H ethyl (S) 5.33 1dimethylamino H ethyl (S) 5.34 1 methylamino H ethyl (S) 5.35 1 ethyl H2-methyl- (S) 76-78 2-propyl 5.36 1 ethyl H cyclopropyl (R, S) oil 5.371 ethyl H cyclohexyl (R, S) oil

Example 6.1

(S)-2-(Ethylsulfonylamino)-3methyl-butyric acidN-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide

(S)-2-(Ethylsulfonylamino)-3-methyl-butyric acidN-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide

21.1 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid and 12 ml ofN-methylmorpholine in 450 ml of tetrahydrofuran are cooled, withstirring, to −20° C. 13.2 ml of isobutyl chloroformate are addeddropwise thereto over a period of 10 minutes. The reaction mixture isthen stirred at −10° C. for 1 hour. The mixture is again cooled to −20°C., and a solution of 26.1 g of2-(4-benzyloxy-3-methoxyphenyl)-ethylamine in 100 ml of tetrahydrofuranis added dropwise thereto over a period of 20 minutes. The reactionmixture is then stirred, without cooling, for 4 hours, the internaltemperature gradually rising to room temperature. The reaction mixtureis then introduced into 400 ml of 2N hydrochloric acid. Extraction iscarried out twice using 500 ml of ethyl acetate each time. The organicphases are washed once with 250 ml of 2N hydrochloric acid, once with250 ml of saturated sodium chloride solution, twice using 250 ml of 2Npotassium hydrogen carbonate solution each time and once with 250 ml ofsaturated sodium chloride solution, dried over magnesium sulfate andconcentrated, yielding (S)-2-(ethylsulfonylamino)-3methyl-butyric acidN-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide, m.p. 140-142° C.,which can be purified further by digestion in 200 ml of tert-butylmethyl ether.

(S)-2-(Ethylsulfonylamino)-3-methyl-butyric acidN-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide

a)

5.1 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid and 5.7 ml ofN-methylmorpholine in 200 ml of tetrahydrofuran are cooled, withstirring, to −20° C. 3.15 ml of isobutyl chloroformate are addeddropwise thereto. When the addition is complete, the reaction mixture isstirred at −10° C. for 40 minutes. The mixture is again cooled to −20°C. 5.0 g of solid 2-(4-hydroxy-3-methoxy-phenyl)-ethylaminehydrochloride are introduced into the reaction mixture. The reactionmixture is stirred, without cooling, for a further 24 hours, theinternal temperature gradually rising to room temperature. The reactionmixture is introduced into 300 ml of 2N hydrochloric acid. Extraction iscarried out twice using 500 ml of ethyl acetate each time. The organicphases are washed twice using 100 ml of saturated sodium chloridesolution each time, dried over magnesium sulfate and concentrated. Theresidue is purified by flash chromatography on silica gel with a mixtureof ethyl acetate/n-hexane 3: 1, yielding(S)-2-(ethylsulfonylamino)-3methyl-butyric acidN-[2-(4-hydroxy-3-methoxyphenyl)-ethyl]-amide in the form of acolourless oil.

b)

14.5 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acidN-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide are dissolved in 420 mlof tetrahydrofuran and, together with 3 g of 5% palladium on activecarbon, shaken in a hydrogenation vessel for 5 hours in a hydrogenatmosphere under normal pressure. The catalyst is then filtered off. Thefiltrate is concentrated. The residue is purified by flashchromatography on silica gel with ethyl acetate/n-hexane 3:1, yielding(S)-2-(ethylsulfonylamino)-3methyl-butyric acidN-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide in the form of acolourless oil.

c)

1.7 g of 2-(4-hydroxy-3-methoxy-phenyl)-ethylamine and 2.1 g of(S)-2-(ethylsulfonylamino)-3-methyl-butyric acid are stirred at roomtemperature for 2 hours together with 4.6 g of(benzotriazol-1-yl)-tris(dimethylamino)phosphonium hexafluorophosphateand 4.5 ml of diisopropylethylamine in 40 ml of dimethylformamide. Thereaction mixture is then introduced into 600 ml of water. Extraction iscarried out twice using 400 ml of ethyl acetate each time. The organicphases are washed twice using 300 ml of water each time and once with200 ml of saturated sodium chloride solution, dried over magnesiumsulfate and concentrated, yielding(S)-2-(ethylsulfonylamino)3-methyl-butyric acidN-[2-(4-hydroxy-3-methoxyphenyl)-ethyl]-amide in the form of a brownoil, which can be purified by chromatography on silica gel with ethylacetate.

The Examples listed in Table 6 are obtained analogously to the aboveExample.

TABLE 6

Conf. Physical No. R₁ R₃ α-C data 6.1 ethyl 2-propyl (S) oil 6.2 ethenyl2-propyl (S) 6.3 methyl 2-propyl (S) m.p. 149-151° C. 6.4 propyl2-propyl (S) oil 6.5 isopropyl 2-propyl (S) oil 6.6 butyl 2-propyl (S)6.7 isobutyl 2-propyl (S) 6.8 allyl 2-propyl (S) 6.92-methyl-2-propen-1-yl 2-propyl (S) oil 6.10 3-chloropropyl 2-propyl (S)m.p. 124-126° C. 6.11 dimethylamino 2-propyl (S) 6.12 diethylamino2-propyl (S) 6.13 methylamino 2-propyl (S) 6.14 methyl ethyl (S) 6.15ethyl ethyl (S) oil 6.16 propyl ethyl (S) 6.17 isopropyl ethyl (S) 6.18dimethylamino ethyl (S) 6.19 methylamino ethyl (S) 6.19 methylaminoethyl (S) 6.20 ethyl 2-methyl- (S) resin 2-propyl 6.21 ethyl cyclo- (R,S) resin propyl 6.22 ethyl cyclo- (R, S) resin hexyl 6.23 cyclopropyl2-propyl (S) oil

Example 7.7

2-[3-Methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamine

3-Methoxy-4-(naphthalen-1-ylmethoxy)-benzaldehyde

5 g of sodium are dissolved in 200 ml of methanol. 30.4 g of vanillinare metered into the resulting solution. The reaction mixture is stirredat room temperature for 30 minutes. 36 g of 1-chloromethylnaphthalene in70 ml of methanol are then added and the reaction mixture is heated atreflux for 6 hours. The mixture is left to stand overnight and thenintroduced into 1 liter of water. Extraction is carried out twice using700 ml of ethyl acetate each time. The organic phases are washed twiceusing 200 ml of ice-cold 2N sodium hydroxide solution each time and oncewith 200 ml of saturated sodium chloride solution, dried over magnesiumsulfate and concentrated, yielding3-methoxy(naphthalen-1-ylmethoxy)-benzaldehyde, which can be purified bychromatography on silica gel with ethyl acetate/n-hexane 1:2 andrecrystallisation from ethyl acetate/n-hexane, m.p. 98-99° C.

1-[2-Methoxy-4-(2-nitro-vinyl)-phenoxymethyl]-naththalene

36 g of 3-methoxy-4-(naphthalen-1-ylmethoxy)-benzaldehyde, 8.7 9 ofammonium acetate and 10 ml of nitromethane are together heated at refluxfor 5 hours in 140 ml of glacial acetic acid. After cooling, thereaction mixture is introduced into 1.5 liters of water. Extraction iscarried out twice using 1 liter of ethyl acetate each time. The organicphases are washed 4 once with 500 ml of water and three times using 400ml of 2N potassium hydrogen carbonate solution each time, dried overmagnesium sulfate and concentrated, yielding1-[2-methoxy-4-(2-nitro-vinyl)-phenoxymethyl]-naphthalene, which can bepurified by chromatography on silica gel with ethyl acetate/n-hexane 1:4and recrystallisation in ethyl acetate/n-hexane, m.p. 120-123° C.

2-[3-Methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamine

10 g of lithium aluminium hydride are placed in 200 ml oftetrahydrofuran; the mixture is stirred at room temperature. 25.8 g of1-[2-methoxy-4-(2-nitro-vinyl)-phenoxymethyl]-naphthalene dissolved in300 ml of tetrahydrofuran are added dropwise thereto over a period of 90minutes. The reaction mixture is heated at reflux for 4 hours. Aftercooling, 40 ml of 1 N sodium hydroxide solution are cautiously addeddropwise, external cooling being effected using an ice bath. When theaddition is complete, the reaction mixture is stirred, without cooling,for one hour, then filtered with suction over Celite and washed with asmall amount of tetrahydrofuran. The filtrate is dried over potassiumcarbonate and concentrated by evaporation, yielding2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamine in the formof a brown oil.

The Examples given in Table 7 are obtained analogously to the aboveExample.

TABLE 7

Comp. Phys. No. R₄ -(R₉)_(p)-A data 7.1 H

oil 7.2 methyl

7.3 H

7.4 H

7.5 H

7.6 H

7.7 H

7.8 H

7.9 H

7.10 H

7.11 H

7.12 H

7.13 H

7.14 H

7.15 H

7.16 H

7.17 H

7.18 H

7.19 H

7.20 H

7.21 H

7.22 H

7.23 H

7.24 H

7.25 H

7.26 H

7.27 H

7.28 H

7.29 H

7.30 H

7.31 H

7.32 H

7.33 H

7.34 H

7.35 H

7.36 H

7.37 H

7.38 H

7.39 H

7.40 H

7.41 H

7.42 H

7.43 H

7.44 H

7.45 H

7.46 H

7.47 H

7.48 H

7.49 H

7.50 H

7.51 H

7.52 H

7.53 H

7.54 H

7.55 H

7.56 H

7.57 H

7.58 H

7.59 H

7.60 H

7.61 H

Example 8.16

(2S,3S)-2-Amino-3-methyl-valeric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide

(2S,3S)-2-(tert-Butoxycarbonyl-amino)-3methyl-valenic acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide

13.9 g of (2S,3S)-2-(tert-butoxycarbonyl-amino)-3-methyl-valeric acid(BOC-L-isoleucine) and 18.5 g of2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamine are stirredat room temperature for two hours together with 25 g of(benzotriazol-1-yl)-tris(dimethylamino)-phosphonium hexafluorophosphateand 155 ml of diisopropylethylamine in 300 ml of dimethylformamide. Thereaction mixture is then introduced into 800 ml of water. Extraction iscarried out twice using 800 ml of ethyl acetate each time. The organicphases are washed twice using 250 ml of 2N hydrochloric acid each time,twice using 250 ml of 2N potassium hydrogen carbonate solution each timeand once with 200 ml of saturated sodium chloride solution, dried overmagnesium sulfate and concentrated, yielding(2S,3S)-2-(tert-butoxy-carbonyl-amino)-3-methyl-valeric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide in theform of a yellowish oil, which can be purified by chromatography onsilica gel.

(2S,3S)-2-Amino-3methyl-valeric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide

12.6 9 of (2S,3S)-2-(tert-butoxycarbonyl-amino)-3-methyl-valeric acidN-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide aredissolved in 100 ml of dioxane. 200 ml of a 4M solution of hydrogenchloride in dioxane are added thereto. The reaction mixture is stirredat room temperature for 24 hours and then 300 ml of water are addedthereto. Extraction is carried out twice using 300 ml of ethyl acetateeach time. The organic phases are washed twice using 150 ml of 2Nhydrochloric acid each time. The combined aqueous extracts are adjustedto a pH value of >8 by the addition of solid potassium carbonate.Extraction is carried out twice using 400 ml of tert-butyl methyl ethereach time. The organic phases are combined, dried over potassiumcarbonate and concentrated, yielding (2S,3S)-2-amino-3-methyl-valericacid N-{2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethyl}-amide inthe form of a yellow oil.

The Examples given in Table 8 are obtained analogously to the aboveExample.

TABLE 8

Comp. Conf Phys No. at α-C n R₂ R₃ R₄ -(R₉)_(p)-A data 8.1 (S) 1 H2-propyl H

8.2 (S) 1 H 2-propyl CH₃

8.3 (S) 1 H ethyl H

8.4 (R, S) 1 H cyclopropyl H

8.5 (R, S) 1 H allyl H

8.6 (S) 1 H

8.7 (S) 1 H 2-butyl H

8.8 (R, S) 1 H cyclo- propyl- methyl H

8.9 (S) 1 H methyl H

8.10 (S) 1 H 2-propyl H

8.11 (S) 1 H 2-propyl H

8.12 (S) 1 H 2-propyl H

8.13 (S) 1 H 2-propyl H

8.14 (S) 1 H 2-propyl H

8.15 (S) 1 H ethyl H

8.16 (S) 1 H 2-butyl H

8.17 (S) 1 H 2-propyl H

8.18 (S) 1 H 2-propyl H

8.19 (S) 1 H 2-propyl H

8.20 (S) 1 H 2-propyl H

8.21 (S) 1 H 2-propyl H

8.22 (S) 1 H 2-propyl H

8.23 (S) 1 H 2-propyl H

8.24 (S) 1 H 2-propyl H

8.25 (S) 1 H 2-propyl H

8.26 (S) 1 H 2-propyl H

8.27 (S) 1 H 2-propyl H

8.28 (S) 1 H 2-propyl H

8.29 (S) 1 H 2-propyl H

8.30 (S) 1 H 2-propyl H

8.31 (S) 1 H 2-propyl H

8.32 (S) 1 H 2-propyl H

8.33 (S) 1 H 2-propyl H

8.34 (S) 1 H 2-propyl H

8.35 (S) 1 H 2-propyl H

8.36 (S) 1 H 2-propyl H

8.37 (S) 1 H 2-propyl H

8.38 (S) 1 H 2-propyl H

8.39 (S) 1 H 2-propyl H

8.40 (S) 1 H 2-propyl H

8.41 (S) 1 H 2-propyl H

8.42 (S) 1 H 2-propyl H

8.43 (S) 1 H 2-propyl H

8.44 (S) 1 H 2-propyl H

8.45 (S) 1 H 2-propyl H

8.46 (S) 1 H 2-propyl H

8.47 (S) 1 H 2-propyl H

8.48 (S) 1 H 2-propyl H

8.49 (S) 1 H 2-propyl H

8.50 (S) 1 H 2-propyl H

8.51 (S) 1 H 2-propyl H

8.52 (S) 1 H 2-propyl H

8.53 (S) 1 H 2-propyl H

8.54 (S) 1 H 2-propyl H

8.55 (S) 1 H 2-propyl H

8.56 (S) 1 H 2-propyl H

8.57 (S) 1 H 2-propyl H

8.58 (S) 1 H 2-propyl H

8.59 (S) 1 H 2-propyl H

8.60 (S) 1 H 2-propyl H

8.61 (S) 1 H 2-propyl H

8.62 (S) 1 H 2-propyl H

8.63 (S) 1 H 2-propyl H

8.64 (S) 1 H 2-propyl H

8.65 (S) 1 H 2-propyl H

8.66 (S) 1 H 2-propyl H

8.67 (S) 1 H 2-propyl H

8.68 (S) 1 H 2-propyl H

8.69 (S) 1 H 2-propyl H

8.70 (S) 1 H 2-propyl H

Formulation Examples for Compounds of Formula I (Throughout, Percentagesare by Weight)

F-1 : Wettable powders a) b) c) a compound of Tables 1 and 2, 25%  50% 75% e.g. Comp. 2.2 sodium lignosulfonate 5% 5% — sodium lauryl sulfate3% —  5% sodium diisobutylnaphthalenesulfonate — 6% 10% octylphenolpolyethylene glycol ether — 2% — (7-8 mol of ethylene oxide) highlydispersed silicic acid 5% 10%  10% kaolin 62%  27%  —

The active ingredient is thoroughly mixed with the adjuvants and themixture is thoroughly ground in a suitable mill, affording wettablepowders which can be diluted with water to give suspensions of anydesired concentration.

F-2: Emulsifiable concentrate a compound of Tables 1 and 2, 10% e.g.Comp. 2.2 octylphenol polyethylene glycol ether  3% (4-5 mol of ethyleneoxide) calcium dodecylbenzenesulfonate  3% castor oil glycol ether  4%(35 mol of ethylene oxide) cyclohexanone 30% xylene mixture 50%

Emulsions of any required concentration can be obtained from thisconcentrate by dilution with water.

F-3: Dusts a) b) a compound of Tables 1 and 2  5%  8% talcum 95% —kaolin — 92%

Ready-for-use dusts are obtained by mixing the active ingredient withthe carrier and grinding the mixture in a suitable mill.

F-4: Extruder granules a compound of Tables 1 and 2 10% sodiumlignosulfonate  2% carboxymethylcellulose  1% kaolin 87%

The active ingredient is mixed and ground with the adjuvants, and themixture is moistened with water. The mixture is extruded and then driedin a stream of air.

F-5: Coated granules a compound of Tables 1 and 2 3% polyethylene glycol(mol. wt. 200) 3% kaolin 94% 

The finely ground active ingredient is uniformly applied, in a mixer, tothe kaolin moistened with polyethylene glycol. Non-dusty coated granulesare obtained in this manner.

F-6: Suspension concentrate a compound of Tables 1 and 2, 40%   e.g.Comp. 2.2 ethylene glycol 10%   nonylphenol polyethylene glycol ether 6%   (15 mol of ethylene oxide) sodium lignosulfonate 10%  carboxymethylcellulose  1%   37% aqueous formaldehyde solution  0.2%silicone oil in the form of a 75% aqueous  0.8% emulsion water 32%  

The finely ground active ingredient is intimately mixed with theadjuvants, giving a suspension concentrate from which suspensions of anydesired dilution can be obtained by dilution with water.

Biological Examples

B-1: Action against Plasmopara Viticola on Vines

a) Residual-protective action

Vine seedlings are sprayed at the 4- to 5leaf stage with a spray mixture(0.02% active ingredient) prepared from a wettable powder formulation ofthe test compound. After 24 hours, the treated plants are infected witha sporangia suspension of the fungus. Fungus infestation is evaluatedafter incubation for 6 days at 95-100% relative humidity and 20° C.

b) Residual-curative Action

Vine seedlings are infected at the 4- to 5-leaf stage with a sporangiasuspension of the fungus. After incubation for 24 hours in a humiditychamber at 95-100% relative humidity and 20° C., the infected plants aredried and sprayed with a spray mixture (0.02% active ingredient)prepared from a wettable powder formulation of the test compound. Afterthe spray coating has dried, the treated plants are placed in thehumidity chamber again. Fungus infestation is evaluated 6 days afterinfection.

Compounds of Tables 1 to 4 exhibit a very good fungicidal action againstPlasmopara viticola on vines. Compounds Nos. inter alia 1.1., 1.7.,1.12., 1.17., 2.1., 2.2., 2.16., 2.30., 2.31. and 2.57 achieve completesuppression of fungus infestation (residual infestation 0 to 5%). On theother hand, Plasmopara infestation on untreated and infected controlplants is 100%.

B-2: Action against Phytophthora on Tomato Plants

a) Residual-protective Action

After a cultivation period of 3 weeks, tomato plants are sprayed with aspray mixture (0.02% active ingredient) prepared from a wettable powderformulation of the test compound. After 48 hours, the treated plants areinfected with a sporangia suspension of the fungus. Fungus infestationis evaluated after incubation of the infected plants for 5 days at90-100% relative humidity and 20° C.

b) Systemic Action

After a cultivation period of 3 weeks, tomato plants are watered with aspray mixture (0.02% active ingredient based on the volume of the soil)prepared from a wettable powder formulation of the test compound. Careis taken that the spray mixture does not come into contact with theparts of the plants that are above the ground. After 96 hours, thetreated plants are infected with a sporangia suspension of the fungus.Fungus infestation is evaluated after incubation of the infected plantsfor 4 days at 90-100% relative humidity and 20° C. Compounds of Tables 1and 2 exhibit a lasting effect (less than 20% fungus infestation).Infestation is prevented virtually completely (0 to 5% infestation) withcompounds Nos. 1.1., 1.7., 1.12., 1.17., 2.1., 2.2., 2.16., 2.30., 2.31.and 2.57. On the other hand, Phytophthora infestation on untreated andinfected control plants is 100%.

B-3: Action against Phytophthora on Potato Plants

a) Residual-protective Action

2-3 week old potato plants (Bintje variety) are sprayed with a spraymixture (0.02% active ingredient) prepared from a wettable powderformulation of the test compound. After 48 hours, the treated plants areinfected with a sporangia suspension of the fungus. Fungus infestationis evaluated after incubation of the infected plants for 4 days at90-100% relative humidity and 20° C.

b) Systemic Action

2-3 week old potato plants (Bintje variety) are watered with a spraymixture (0.02% active ingredient based on the volume of the soil)prepared from a wettable powder formulation of the test compound. Careis taken that the spray mixture does not come into contact with theparts of the plants that are above the ground. After 48 hours, thetreated plants are infected with a sporangia suspension of the fungus.Fungus infestation is evaluated after incubation of the infected plantsfor 4 days at 90-100% relative humidity and 20° C.

Compounds of Tables 1 and 2 exhibit a lasting effect (less than 20%fungus infestation). Infestation is prevented virtually completely (0 to5% infestation) with compounds Nos. 1.1., 1.7., 1.12., 1.17., 2.1.,2.2., 2.16., 2.30., 2.31. and 2.57. On the other hand, Phytophthorainfestation on untreated and infected control plants is 100%.

What is claimed is:
 1. A compound of formula I:

wherein n is a number zero or one; and R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted by C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₁-C₆alkynyloxycarbonyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl or a group NR₁₁R₁₂; wherein R₁₁ and R₁₂ are each independently of the other hydrogen, C₁-C₆alkyl or together are tetra- or penta-methylene; R₂ and R₃ are each independently of the other hydrogen; C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl or wherein the two groups R₂ and R₃ together with the carbon atom to which they are bonded form a three- to eight-membered ring; R₄, R₅, R₆ and R₇ are identical or different and are each independently of the others hydrogen or C₁-C₄alkyl; R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl; p is a number zero or one; R₉ is C₁-C₆alkylene; and A is unsubstituted or mono- or poly-substituted heteroaryl or unsubstituted or mono- or poly-substituted aryl containing more than 6 carbon atoms.
 2. A compound according to claim 1, wherein: A is naphthyl, heteroaryl that is formed from one or two five- or six-membered rings and that may contain from 1 to 4 identical or different hetero atoms selected from nitrogen, oxygen and sulfur, wherein that naphthyl or heteroaryl may carry from 1 to 4 identical or different substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, it being possible for the hydrogen atoms of those groups to have been replaced by one or more identical or different halogen atoms; C₁-C₈alkoxy, C₃-C₈alkenyloxy, C₃-C₈alkynyloxy, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, formyl, C₂-C₈alkanoyl, hydroxy, halogen, cyano, nitro, amino, C₁-C₈alkylamino, C₁-C₈dialkylamino, carboxy, C₁-C₈alkoxycarbonyl, C₃-C₈alkenyloxycarbonyl and C₃-C₈alkynyloxycarbonyl.
 3. A compound according to claim 2, wherein: A is naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, quinoxalinyl, unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₂-C₈alkenyl, C₂-C₈alkynyl, C₃-C₈cycloalkyl, C₃-C₈cycloalkyl-C₁-C₄alkyl, phenyl, phenyl-C₁-C₄alkyl, it being possible for the hydrogen atoms of those groups to have been replaced by one or more identical or different halogen atoms; C₁-C₈alkoxy, C₃-C₈alkenyloxy, C₃-C₈alkynyloxy, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfonyl, formyl, C₂-C₈alkanoyl, hydroxy, halogen, cyano, nitro, amino, C₁-C₈alkylamino, C₁-C₈dialkylamino, carboxy, C₁-C₈alkoxycarbonyl, C₃-C₈alkenyloxycarbonyl and C₃-C₈alkynyloxycarbonyl.
 4. A compound according to claim 3, wherein: p is a number one; A is naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, quinoxalinyl, unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, phenyl, phenyl-C₁-C₄alkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano and nitro.
 5. A compound according to claim 4, wherein: R₉ is —CH₂—; A is naphthyl, furyl, thienyl, thiazolyl, oxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, unsubstituted or substituted by from 1 to 3 substituents selected from: C₁-C₈alkyl, C₁-C₈haloalkyl, phenyl, phenyl-C₁-C₄alkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio, C₁-C₈haloalkylthio, halogen, cyano and nitro.
 6. A compound according to claim 3, wherein: n is a number one, R₁ is C₁-C₁₂alkyl that is unsubstituted or may be substituted by C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl or a group NR₁₁R₁₂; wherein R₁₁ and R₁₂ are each independently of the other hydrogen, C₁-C₆alkyl or together are tetra- or penta-methylene; R₂ is hydrogen; R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted by hydroxy, C₁-C₄alkoxy, mercapto or by C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl.
 7. A compound according to claim 6, wherein: R₁ is C₁-C₄alkyl or dimethylamino; R₃ is C₃-C₄alkyl; R₄ is hydrogen or methyl; R₈ is C₁-C₂alkyl.
 8. A process for the preparation of a compound of formula I according to claim 1, which process comprises a) reacting a substituted amino acid of formula II

wherein the radicals R₁, R₂ and R₃ and n are as defined in claim 1, or a carboxy-activated 4 derivative thereof, if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent, at temperatures of from −80 to +150° C., with an amine of formula III

wherein R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined in claim 1; or b) oxidising a compound of formula I′

wherein R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined in claim 1, with the proviso that none of the substituents R₁, R₂, R₃ and A contains a thiol or alkylthio group, with an oxidising agent, in an inert diluent, optionally in the presence of an acid or optionally in the presence of a base, at temperatures of from −80 to +150° C.; or c) reacting a compound of formula IV

wherein R₁, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ and n are as defined in claim 1, with a compound of formula V Y—(R₉)p—A  V, wherein R₉, p and A are as defined in claim 1 and wherein Y is a leaving group, in an inert solvent, if desired in the presence of an acid-binding agent, at temperatures of from −80 to +200° C.; or d) reacting a sulfonic acid or sulfinic acid, or a sulfonic acid or sulfinic acid derivative, of formula VI

wherein R₁ and n are as defined in claim 1 and wherein X is an OH group or a leaving group, respectively, with an amine of formula VII

wherein R₂, R₃, R₄,l R₅, R₆, R₇, R₈, R₉, p and A are as defined in claim 1, in an inert solvent, if desired in the presence of an acid-binding agent, at temperatures of from −80 to +150° C.
 9. A composition for controlling and preventing pests, comprising a compound according to claim 1 as active ingredient together with a suitable carrier.
 10. A method of controlling and preventing an infestation of crop plants by phytopathogenic microorganisms, which comprises the application of a compound of formula I according to claim 1 as active ingredient to the plant, to parts of plants or to the locus thereof.
 11. A method according to claim 10, wherein the phytopathogenic microorganisms are fungal organisms.
 12. A compound of formula III

wherein R₄, R₅, R₆, R₇, R₈, R₉, p and A are as defined in claim
 1. 13. A process for the preparation of a compound of formula III according to claim 12, which process comprises using

wherein Step A is the alkylation of a phenol with a compound of formula V; Step B is the reaction of an aromatic aldehyde with nitromethane; Step C is the reduction of an unsaturated nitrogen compound; Step D is the reaction of an aldehyde or a ketone with hydroxylamine or a hydroxylamine salt; Step E is the hydrolysis of a lower alkyl ester, and Step F is the reaction of a carboxylic acid or an activated carboxylic acid derivative with hydrazoic acid or with a salt of that acid.
 14. A compound of formula VII

wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, p and A are as define in claim
 1. 15. A process for the preparation of a compound of formula VII according to claim 14, which comprises carrying out the following reaction sequence

wherein the reaction of the amino acid derivative of formula XIII, or of a carboxy-activated derivative thereof, with an amine of formula XII is carried out if desired in the presence of a catalyst, if desired in the presence of an acid-binding agent and if desired in the presence of a diluent; and the reaction of a compound of formula XIV with a compound of formula V is carried out if desired in the presence of an acid-binding agent and if desired in the presence of an inert diluent at temperatures of from −80 to +200° C.; and then the acid hydrolysis of a compound of formula XV with an inorganic or organic acid is carried out if desired in the presence of an inert diluent, at temperatures of from −40 to +150° C. 